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New Insights into Human Mesenchymal Stem Cells

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Dear Colleagues,

MSCs, multipotent and non-hematopoietic mesenchymal stem/stromal cells, were first described by hematologist A. Friedenstein more than 50 years ago. Since then, their roles in various tissue-related processes, such as homeostasis, differentiation, signaling, and many others, have been investigated. Since MSCs are present in all organs and tissues, they play important roles in tissue regeneration processes as well as in the development of many chronic autoimmune or degenerative diseases that have been shown to be related to the dysfunction or depletion of MSCs.

Recently, multiple studies in vitro, as well as in vivo, have demonstrated MSCs regulating basic cellular processes, such as inflammation, oxidative stress, angiogenesis, etc., having broad therapeutic applications due to their low immune rejection. However, despite the direct use of MSCs in cell-based therapy, MSCs also act as paracrine regulators, i.e., MSCs secrete cytokines, hormones, extracellular vesicles, and other compounds, preventing the inconveniences associated with cell-based therapy, such as cell survival, heterogeneity, and functioning.

In addition, the multiple cell–cell-based and paracrine effects of MSCs and/or subpopulations also allow them to be investigated in combination with various tissue engineering scaffolds, hydrogels, or other cell–matrix biomodel systems in vitro and in vivo, adjusting various types of intracellular and extracellular stimuli in order to improve therapeutic applicability. The prevalence and multifunctionality of MSCs still do not lose scientific interest, forcing the search for new methods of investigation.

Dr. Daiva Bironaité
Guest Editor

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Keywords

mesenchymal stem/stromal cells (MSCs)
proliferation
differentiation
death/survival
internal and external stimuli
therapeutic drugs
subpopulations
cell–cell and cell–matrix interactions

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14 pages, 7077 KiB

Open AccessArticle

Mesenchymal Stem Cells Increase Drug Tolerance of A431 Cells Only in 3D Spheroids, Not in 2D Co-Cultures

by Flóra Vajda, Áron Szepesi, Zsuzsa Erdei, Edit Szabó, György Várady, Dániel Kiss, László Héja, Katalin Német, Gergely Szakács and András Füredi

Int. J. Mol. Sci. 2024, 25(8), 4515; https://doi.org/10.3390/ijms25084515 - 20 Apr 2024

Viewed by 313

Abstract

Mesenchymal stem cells (MSCs) are an integral part of the tumor microenvironment (TME); however, their role is somewhat controversial: conflicting reports suggest that, depending on the stage of tumor development, MSCs can either support or suppress tumor growth and spread. Additionally, the influence of MSCs on drug resistance is also ambiguous. Previously, we showed that, despite MSCs proliferating significantly more slowly than cancer cells, there are chemotherapeutic drugs which proved to be similarly toxic to both cell types. Here we established 2D co-cultures and 3D co-culture spheroids from different ratios of GFP-expressing, adipose tissue-derived MSCs and A431 epidermoid carcinoma cells tagged with mCherry to investigate the effect of MSCs on cancer cell growth, survival, and drug sensitivity. We examined the cytokine secretion profile of mono- and co-cultures, explored the inner structure of the spheroids, applied MSC-(nutlin-3) and cancer cell-targeting (cisplatin) treatments separately, monitored the response with live-cell imaging and identified a new, double-fluorescent cell type emerging from these cultures. In 2D co-cultures, no effect on proliferation or drug sensitivity was observed, regardless of the changes in cytokine secretion induced by the co-culture. Conversely, 3D spheroids developed a unique internal structure consisting of MSCs, which significantly improved cancer cell survival and resilience to treatment, suggesting that physical proximity and cell–cell connections are required for MSCs to considerably affect nearby cancer cells. Our results shed light on MSC–cancer cell interactions and could help design new, better treatment options for tumors. Full article

(This article belongs to the Special Issue New Insights into Human Mesenchymal Stem Cells)

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20 pages, 2146 KiB

Open AccessArticle

Mesenchymal Stromal Cells from Perinatal Tissues as an Alternative for Ex Vivo Expansion of Hematopoietic Progenitor and Stem Cells from Umbilical Cord Blood

by Ximena Bonilla, Ana Milena Lara, Manuela Llano-León, David A. López-González, David G. Hernández-Mejía, Rosa Helena Bustos, Bernardo Camacho-Rodríguez and Ana-María Perdomo-Arciniegas

Int. J. Mol. Sci. 2023, 24(21), 15544; https://doi.org/10.3390/ijms242115544 - 24 Oct 2023

Cited by 1 | Viewed by 1036

Abstract

Umbilical cord blood (UCB) serves as a source of hematopoietic stem and progenitor cells (HSPCs) utilized in the regeneration of hematopoietic and immune systems, forming a crucial part of the treatment for various benign and malignant hematological diseases. UCB has been utilized as an alternative HSPC source to bone marrow (BM). Although the use of UCB has extended transplantation access to many individuals, it still encounters significant challenges in selecting a histocompatible UCB unit with an adequate cell dose for a substantial proportion of adults with malignant hematological diseases. Consequently, recent research has focused on developing ex vivo expansion strategies for UCB HSPCs. Our results demonstrate that co-cultures with the investigated mesenchymal stromal cells (MSCs) enable a 10- to 15-fold increase in the cellular dose of UCB HSPCs while partially regulating the proliferation capacity when compared to HSPCs expanded with early acting cytokines. Furthermore, the secretory profile of UCB-derived MSCs closely resembles that of BM-derived MSCs. Moreover, both co-cultures exhibit alterations in cytokine secretion, which could potentially impact HSPC proliferation during the expansion process. This study underscores the fact that UCB-derived MSCs possess a remarkably similar supportive capacity to BM-derived MSCs, implying their potential use as feeder layers in the ex vivo expansion process of HSPCs. Full article

(This article belongs to the Special Issue New Insights into Human Mesenchymal Stem Cells)

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